Tandem pore domain potassium channel - are constitutively open or possess high basal activation, such as the "resting potassium channels" or "leak channels" that set the negative membrane potential of neurons. When open, they allow potassium ions to cross the membrane at a rate which is nearly as fast as their diffusion through bulk water.

There are over 80 mammaliangenes that encode potassium channel subunits. The pore-forming subunits of potassium channels have a homo- or heterotetrameric arrangement. Four subunits are arranged around a central pore. All potassium channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium selectivity.

Potassium ion channels remove the hydration shell from the
ion when it enters the selectivity filter. The selectivity filter is
formed by five residues (TVGYG-in procaryotic species) from each subunit which
have their electro-negative carbonyl oxygen atoms aligned
towards the centre of the filter pore and form an anti-prism
similar to a water solvating shell around each potassium
binding site. The distance between the carbonyl oxygens and
potassium ions in the binding sites of the selectivity filter is the
same as between water oxygens in the first hydration shell and
a potassium ion in water solution. The selectivity filter opens
towards the extracellular solution, exposing four carbonyl
oxygens in a glycine residue (Gly79 in KcsA). The next residue towards the extracellular side of
the protein is the negatively charged Asp80 (KcsA). This residue form together with the five
filter residues the pore that connects the water filled cavity in
the centre of the protein with the extracellular solution.

The carbonyl oxygens are strongly electro-negative and cation
attractive. The filter can accommodate potassium ions at 4 sites
usually labelled S1 to S4 starting at the extracellular side. In
addition one ion can bind in the cavity at a site called SC or
one or more ions at the extracellular side at more
or less well defined sites called S0 or Sext. Several different
occupancies of these sites are possible. Since the X-ray
structures are averages over many molecules, it is, however,
not possible to deduce the actual occupancies directly from
such a structure. In general, there is some disadvantage due to
electrostatic repulsion to have two neighbouring sites occupied
by ions. The mechanism for ion translocation in KcsA has been
studied extensively by simulation techniques. A complete map of the free energies of the
24=16 states (characterised by the occupancy of the S1, S2, S3
and S4 sites) has been calculated with molecular dynamics simulations resulting in the
prediction of an ion conduction mechanism in which the two
doubly occupied states (S1, S3) and (S2, S4) play an essential
role. The two extracellular states, Sext and
S0, were found in a better resolved structure of KcsA at high
potassium concentration. In free energy calculations the
entire ionic pathway from the cavity, through the four filter
sites out to S0 and Sext was covered in MD simulations.
The amino acids sequence of the selectivity filter of
potassium ion channels is conserved with the exception that
an isoleucine residue in eukaryotic potassium ion channels
often is substituted with a valine residue in prokaryotic
channels.